Inhibitors of bruton's tyrosine kinase
AssigneePharmacyclics, Inc.
InventorsLee HONIGBERG, Erik VERNER, Joseph J. BUGGY, David LOURY, Wei CHEN
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Abstract
Described herein are irreversible kinase inhibitor compounds, methods for synthesizing such irreversible inhibitors, and methods for using such irreversible inhibitors in the treatment of diseases. Further described herein are methods, assays and systems for determining an appropriate irreversible inhibitor of a protein, including a kinase.
Claims27
-100. (canceled)
A pharmaceutical composition comprising a compound of Formula (B5), an anticancer agent, and a pharmaceutically acceptable excipient, wherein the compound of Formula (B5) has the structure:
- wherein:
- Y is a 4-, 5-, 6-membered cycloalkylene ring;
- each Ra is independently H, halogen, —CF3, —CN, —NO2, OH, NH2, -La-(substituted or unsubstituted alkyl), -La-(substituted or unsubstituted alkenyl), -La-(substituted or unsubstituted heteroaryl), or -La-(substituted or unsubstituted aryl), wherein La is a bond, O, S, —S(═O), —S(═O)2, NH, C(O), CH2, —NHC(O)O, —NHC(O), or —C(O)NH;
- G is
- R2 is selected from H, lower alkyl, and substituted lower alkyl;
- R6, R7 and R8 are independently selected from among H, lower alkyl or substituted lower alkyl, lower heteroalkyl or substituted lower heteroalkyl, substituted or unsubstituted lower cycloalkyl, and substituted or unsubstituted lower heterocycloalkyl;
- R12 is H or lower alkyl;
- or
- Y and R12 taken together form a 4-, 5-, or 6-membered heterocyclic ring;
- or
- pharmaceutically acceptable salts thereof.
A method for treating a blood cell cancer comprising administering to a subject in need thereof a therapeutically effective amount of an anticancer agent and a compound of Formula (B5):
- wherein:
- Y is a 4-, 5-, 6-membered cycloalkylene ring;
- each Ra is independently H, halogen, —CF3, —CN, —NO2, OH, NH2, -La-(substituted or unsubstituted alkyl), -La-(substituted or unsubstituted alkenyl), -La-(substituted or unsubstituted heteroaryl), or -La-(substituted or unsubstituted aryl), wherein La is a bond, O, S, —S(═O), —S(═O)2, NH, C(O), CH2, —NHC(O)O, —NHC(O), or —C(O)NH;
- G is
- R2 is selected from H, lower alkyl, and substituted lower alkyl;
- R6, R7 and R8 are independently selected from among H, lower alkyl or substituted lower alkyl, lower heteroalkyl or substituted lower heteroalkyl, substituted or unsubstituted lower cycloalkyl, and substituted or unsubstituted lower heterocycloalkyl;
- R12 is H or lower alkyl;
- or
- Y and R12 taken together form a 4-, 5-, or 6-membered heterocyclic ring;
- or
- pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.